For decades, Moore's Law and its partner Dennard Scaling have driven technology trends that have enabled exponential performance improvements in computer systems at manageable power dissipation. With the slowing of Moore/Dennard improvements, designers have turned to a range of approaches for extending scaling of computer systems performance and power efficiency. Unfortunately, these scaling gains come at the expense of degraded hardware-software abstraction layers, increased complexity at the hardware-software interface, and increased challenges for software reliability, interoperability, and performance portability This talk will explore the way forward for computer systems designers in this "Post-ISA" era of shifting abstractions. The talk will cover hardware and software design opportunities, methods for formal verification, and a look into the role of future technologies including Quantum Computing.